A rationally designed synthetic antimicrobial peptide against Pseudomonas-associated corneal keratitis: Structure-function correlation

Sk Abdul Mohid; Prerana Sharma; Amani Alghalayini; Tripti Saini; Debarun Datta; Mark D P Willcox; Haydar Ali; Sreyan Raha; Achintya Singha; DongKuk Lee; Nirakar Sahoo; Charles G Cranfield; Sanhita Roy; Anirban Bhunia

doi:10.1016/j.bpc.2022.106802

A rationally designed synthetic antimicrobial peptide against Pseudomonas-associated corneal keratitis: Structure-function correlation

Sk Abdul Mohid
, Prerana Sharma
, Amani Alghalayini
, Tripti Saini
, Debarun Datta
, Mark D P Willcox
, Haydar Ali
, Sreyan Raha
, Achintya Singha
, DongKuk Lee
, Nirakar Sahoo
, Charles G Cranfield
, Sanhita Roy
, Anirban Bhunia

Department of Biophysics, Bose Institute, EN 80, Sector V, Bidhan Nagar, Kolkata 700091, India.
Prof Brien Holden Eye Research Centre, L V Prasad Eye Institute, Hyderabad-500034, India.
School of Life Science, University of Technology Sydney, Ultimo, NSW 2007, Australia.
Department of Biology, The University of Texas Rio Grande Valley, Edinburg, TX 78539, USA.
School of Optometry and Vision Science, University of New South Wales, Sydney, NSW 2052, Australia
Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032. India.
Department of Physics, Bose Institute, Kolkata 700009, India.
Seoul National University of Science and Technology, Seoul 01811, Republic of Korea.
Department of Biophysics, Bose Institute, EN 80, Sector V, Bidhan Nagar, Kolkata 700091, India. Electronic address: [email protected].

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

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Abstract

Contact lens wearers are at an increased risk of developing Pseudomonas-associated corneal keratitis, which can lead to a host of serious ocular complications. Despite the use of topical antibiotics, ocular infections remain a major clinical problem, and a strategy to avoid Pseudomonas-associated microbial keratitis is urgently required. The hybrid peptide VR18 (VARGWGRKCPLFGKNKSR) was designed to have enhanced antimicrobial properties in the fight against Pseudomonas-induced microbial keratitis, including contact lens-related keratitis. In this paper, VR18's modes of action against Pseudomonas membranes were shown by live cell Raman spectroscopy, live cell NMR, live-cell fluorescence microscopy and measures taken using sparsely tethered bilayer lipid membrane bacterial models to be via a bacterial-specific membrane disruption mechanism. The high affinity and selectivity of the peptide were then demonstrated using in vivo, in vitro and ex vivo models of Pseudomonas infection. The extensive data presented in this work suggests that topical employment of the VR18 peptide would be a potent therapeutic agent for the prevention or remedy of Pseudomonas-associated microbial keratitis.

Original language	English
Article number	106802
Number of pages	14
Journal	Biophysical Chemistry
Volume	286
Early online date	22 Mar 2022
DOIs	https://doi.org/10.1016/j.bpc.2022.106802
Publication status	Published - 1 Jul 2022

Bibliographical note

© 2022 Elsevier B.V. This accepted manuscript version is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License https://creativecommons.org/licenses/by-nc-nd/4.0/

Keywords

Antimicrobial peptide (AMP)
Bacterial keratitis
Contact lens
Nuclear magnetic resonance (NMR)
Pseudomonas aeruginosa

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10.1016/j.bpc.2022.106802

Mohid Sharma Alghalayini et al_pre_proof_1-s2.0-S0301462222000448-main
© 2022 Elsevier B.V. This accepted manuscript version is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License https://creativecommons.org/licenses/by-nc-nd/4.0/
Accepted author manuscript, 1.51 MBLicence: CC BY-NC-ND 4.0

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Mohid, S. A., Sharma, P., Alghalayini, A., Saini, T., Datta, D., Willcox, M. D. P., Ali, H., Raha, S., Singha, A., Lee, D., Sahoo, N., Cranfield, C. G., Roy, S., & Bhunia, A. (2022). A rationally designed synthetic antimicrobial peptide against Pseudomonas-associated corneal keratitis: Structure-function correlation. Biophysical Chemistry, 286, Article 106802. https://doi.org/10.1016/j.bpc.2022.106802

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abstract = "Contact lens wearers are at an increased risk of developing Pseudomonas-associated corneal keratitis, which can lead to a host of serious ocular complications. Despite the use of topical antibiotics, ocular infections remain a major clinical problem, and a strategy to avoid Pseudomonas-associated microbial keratitis is urgently required. The hybrid peptide VR18 (VARGWGRKCPLFGKNKSR) was designed to have enhanced antimicrobial properties in the fight against Pseudomonas-induced microbial keratitis, including contact lens-related keratitis. In this paper, VR18's modes of action against Pseudomonas membranes were shown by live cell Raman spectroscopy, live cell NMR, live-cell fluorescence microscopy and measures taken using sparsely tethered bilayer lipid membrane bacterial models to be via a bacterial-specific membrane disruption mechanism. The high affinity and selectivity of the peptide were then demonstrated using in vivo, in vitro and ex vivo models of Pseudomonas infection. The extensive data presented in this work suggests that topical employment of the VR18 peptide would be a potent therapeutic agent for the prevention or remedy of Pseudomonas-associated microbial keratitis.",

keywords = "Antimicrobial peptide (AMP), Bacterial keratitis, Contact lens, Nuclear magnetic resonance (NMR), Pseudomonas aeruginosa",

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note = "{\textcopyright} 2022 Elsevier B.V. This accepted manuscript version is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License https://creativecommons.org/licenses/by-nc-nd/4.0/",

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Mohid, SA, Sharma, P, Alghalayini, A, Saini, T, Datta, D, Willcox, MDP, Ali, H, Raha, S, Singha, A, Lee, D, Sahoo, N, Cranfield, CG, Roy, S & Bhunia, A 2022, 'A rationally designed synthetic antimicrobial peptide against Pseudomonas-associated corneal keratitis: Structure-function correlation', Biophysical Chemistry, vol. 286, 106802. https://doi.org/10.1016/j.bpc.2022.106802

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AU - Mohid, Sk Abdul

AU - Sharma, Prerana

AU - Alghalayini, Amani

AU - Saini, Tripti

AU - Datta, Debarun

AU - Willcox, Mark D P

AU - Ali, Haydar

AU - Raha, Sreyan

AU - Singha, Achintya

AU - Lee, DongKuk

AU - Sahoo, Nirakar

AU - Cranfield, Charles G

AU - Roy, Sanhita

AU - Bhunia, Anirban

N1 - © 2022 Elsevier B.V. This accepted manuscript version is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License https://creativecommons.org/licenses/by-nc-nd/4.0/

PY - 2022/7/1

Y1 - 2022/7/1

N2 - Contact lens wearers are at an increased risk of developing Pseudomonas-associated corneal keratitis, which can lead to a host of serious ocular complications. Despite the use of topical antibiotics, ocular infections remain a major clinical problem, and a strategy to avoid Pseudomonas-associated microbial keratitis is urgently required. The hybrid peptide VR18 (VARGWGRKCPLFGKNKSR) was designed to have enhanced antimicrobial properties in the fight against Pseudomonas-induced microbial keratitis, including contact lens-related keratitis. In this paper, VR18's modes of action against Pseudomonas membranes were shown by live cell Raman spectroscopy, live cell NMR, live-cell fluorescence microscopy and measures taken using sparsely tethered bilayer lipid membrane bacterial models to be via a bacterial-specific membrane disruption mechanism. The high affinity and selectivity of the peptide were then demonstrated using in vivo, in vitro and ex vivo models of Pseudomonas infection. The extensive data presented in this work suggests that topical employment of the VR18 peptide would be a potent therapeutic agent for the prevention or remedy of Pseudomonas-associated microbial keratitis.

AB - Contact lens wearers are at an increased risk of developing Pseudomonas-associated corneal keratitis, which can lead to a host of serious ocular complications. Despite the use of topical antibiotics, ocular infections remain a major clinical problem, and a strategy to avoid Pseudomonas-associated microbial keratitis is urgently required. The hybrid peptide VR18 (VARGWGRKCPLFGKNKSR) was designed to have enhanced antimicrobial properties in the fight against Pseudomonas-induced microbial keratitis, including contact lens-related keratitis. In this paper, VR18's modes of action against Pseudomonas membranes were shown by live cell Raman spectroscopy, live cell NMR, live-cell fluorescence microscopy and measures taken using sparsely tethered bilayer lipid membrane bacterial models to be via a bacterial-specific membrane disruption mechanism. The high affinity and selectivity of the peptide were then demonstrated using in vivo, in vitro and ex vivo models of Pseudomonas infection. The extensive data presented in this work suggests that topical employment of the VR18 peptide would be a potent therapeutic agent for the prevention or remedy of Pseudomonas-associated microbial keratitis.

KW - Antimicrobial peptide (AMP)

KW - Bacterial keratitis

KW - Contact lens

KW - Nuclear magnetic resonance (NMR)

KW - Pseudomonas aeruginosa

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DO - 10.1016/j.bpc.2022.106802

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SN - 0301-4622

VL - 286

JO - Biophysical Chemistry

JF - Biophysical Chemistry

M1 - 106802

ER -

A rationally designed synthetic antimicrobial peptide against Pseudomonas-associated corneal keratitis: Structure-function correlation

Abstract

Bibliographical note

Keywords

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